Osteoclastogenesis during infective exacerbations in patients with cystic fibrosis

RATIONALE: Adults with cystic fibrosis (CF) are at increased risk of developing osteoporosis. During infective exacerbations, increased production of proinflammatory cytokines and markers of bone resorption have been reported. OBJECTIVE: The aim of this study is to investigate the growth and proliferation of potential osteoclast precursor cells before, during, and after intravenous antibiotic treatment of infective exacerbations in patients with CF. METHODS: Hematopoietic precursor cell growth was examined using colony formation assays using Methocult culture medium. Circulating potential osteoclast precursors were identified using four-color flow cytometry by CD14, CD33, CD34, and CD45 expression. RESULTS: At the start of an infective exacerbation increases in hematopoietic precursor colony formation (15.42 colonies/10(5) cells plated, p = 0.025), proliferation (28.5%, p < 0.001), and the numbers of circulating potential osteoclast precursors (6.5%, p < 0.001) were seen in comparison with baseline levels. These increases declined after treatment with intravenous antibiotics to a level close to baseline. CONCLUSIONS: The results demonstrate an increase in the production of potential osteoclast precursors in the peripheral blood during CF infective exacerbations. This may result in increased bone resorption and contribute to bone loss in patients with CF.     

C-reactive protein in acute pulmonary exacerbations of patients with cystic fibrosis

C-reactive protein (CRP) concentrations were evaluated in 9 cystic fibrosis (CF) patients with acute pulmonary exacerbations and 14 patients with acute exacerbations of asthma without any symptoms of an acute infection. CRP concentrations were serially evaluated over the course of therapy in CF patients and compared with pulmonary function tests (PFTs) and clinical scores. CF patients were treated with aerosolized bronchodilators, intravenous fluids, and chest physiotherapy for 48 hours. Intravenous antibiotic therapy was added after 48 hours. Initial CRP concentrations differed significantly between patients with CF and those with asthma. CRP concentrations were elevated in 7 of 9 CF patients versus 3 of 14 asthma patients (P < 0.02). In CF patients, CRP concentrations did not correlate with PFTs (except on day 0) or clinical scores. Frequently PFTs and clinical scores continued to improve after CRP levels had reached their lowest concentrations. CRP concentrations decreased only after the addition of antibiotic therapy. Pediatr Pulmonol. 1995; 20:215–219 . © 1995 Wiley-Liss, Inc.     

Comparison of the effects of nebulized terbutaline with intravenous enprofylline in patients with acute asthma

We compared the bronchodilating effects of intravenously administered enprofylline (2 mg/kg) with nebulized terbutaline (10 mg) in patients presenting to hospital with acute asthma in a multicenter double-blind parallel study. One hundred twenty three patients were randomized into the study, and 69 of these fulfilled the inclusion criteria and a retrospective time to study entry criterion; 34 received enprofylline and 35 received terbutaline. There was no significant difference in maximum increase in forced expired volume in 1 second (FEV1) between the enprofylline group (0.24 +/- 0.33 L) and the terbutaline group (0.25 +/- 0.28 L) (p greater than 0.05), nor for the increase in FEV1 over the 1-hour study period. Tremor was reported more in the group receiving terbutaline, and nausea was reported more in the group receiving enprofylline. Two patients experienced hypotension and one patient had a vasovagal episode with enprofylline treatment. Both agents acted as bronchodilators with similar efficacy in patients with acute asthma in this study.     

Predictive value of pulmonary function testing during pulmonary exacerbations in cystic fibrosis

The optimal duration of therapy for acute exacerbations of cystic fibrosis (CF) has not been defined, and the utility of serial pulmonary function testing in predicting the duration of therapy has yet to be established. In a review of 90 pulmonary exacerbations of 39 patients with CF requiring hospitalization, we found that 72% of the patients recovered following 2 weeks of intravenous antibiotics and aggressive chest physiotherapy, and that 28% required an extended third week of therapy. Recovery was delayed in patients with more severe chronic pulmonary disease, but the rate of improvement was independent of the degree of pulmonary deterioration with the acute exacerbation. A 40% recovery of FEV, at 1 week was found to correlate significantly with the duration of hospitalization in the 90 patients. When prospectively applied to a second series of consecutively hospitalized patients with CF, 25/28 patients admitted for 2 weeks demonstrated > 40% improvement in FEV, at 1 week, as compared to 5/10 patients subsequently treated for ≤3 weeks (P = 0.030). The predictive values for 2- or 3-week hospitalizations with 1-week interval recovery of > 40% or > 40% in FEV, were 79% and 62%, respectively. These findings suggest that the response to intensive therapy in CF exacerbations is variable and that improvements in pulmonary function after 1 week of therapy may be used to predict the subsequent duration of therapy in the majority of CF patients with pulmonary exacerbations. Pediatr Pulmonol. 1993; 16:227–235. © 1993 Wiley-Liss, Inc.     

Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis.

OBJECTIVE: To compare the health-related quality of life (HRQOL) of people with cystic fibrosis (CF) to the general population, and to determine the relationship between HRQOL and clinical and demographic factors. DESIGN: Cross-sectional analysis of observational cohort. SETTING: Outpatient clinics of a Midwestern CF center. SUBJECTS: One hundred sixty-two subjects with CF aged 5 to 45 years. MAIN OUTCOME MEASURES: Physical and psychosocial summary scores and individual scale scores for the Child Health Questionnaire and Short Form-36. RESULTS: Compared with the general population, people with CF reported similar scores for most psychosocial measures, but lower scores for most physical measures, with the lowest scores on the general health perceptions scale. In multivariable analyses, pulmonary exacerbations in the past 6 months were strongly associated with the physical (p = 0.001) and psychosocial (p = 0.0003) scores. The physical score fell, on average, 6 points per exacerbation and the psychosocial score fell 3 points. Lung function, nutrition, 6-min walk distance, age, gender, and insurance status were not significantly associated with HRQOL in this study population. Those who declined to participate had significantly lower FEV(1) percent predicted and nutritional indexes. Our findings may not be generalizable to the entire CF population. CONCLUSION: Recent pulmonary exacerbations have a profound negative impact on HRQOL that is not explained by differences in lung function, nutritional status, or demographic factors.     

Home versus hospital intravenous antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis

To compare the effectiveness of home versus hospital intravenous (IV) antibiotic therapy for acute pulmonary exacerbations in children with cystic fibrosis (CF). A retrospective chart review was performed of 143 encounters for pulmonary exacerbations in 50 patients with CF. All encounters were categorized into two groups based on location of completion of antibiotic therapy: hospital group completed treatment in hospital (n = 64), home group completed treatment at home (n = 79). Percent change was calculated for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced expiratory flow rate between 25 percent and 75 percent of vital capacity (FEF(25-75%)), maximum forced expiratory flow (FEF(max)), oxygen saturation (O2 SAT), and weight. Means of percent change (PC) from the beginning to the end of IV antibiotic treatment in outcome variables were compared. Total duration of treatment was compared between the two groups. The two groups had no significant differences at baseline in all outcome variables. Treatment of exacerbations in both groups resulted in significant improvement of lung function, O2 SATS, and weight (P 相似文献   

A comparison of pulmonary exacerbations with single and multiple organisms in patients with cystic fibrosis and chronic Burkholderia cepacia infection

STUDY OBJECTIVES: To compare pulmonary exacerbations with single and multiple organisms in patients with chronic Burkholderia cepacia infection. DESIGN: Data was collected over a 23-month period and for each of the patients two episodes of pulmonary exacerbation were identified, one with B. cepacia isolated as the sole respiratory pathogen and the other with one or more coinfecting organisms grown from the sputum culture. SETTING: Regional tertiary referral center for Respiratory Medicine and Adult Cystic Fibrosis Center for Northern Ireland, Belfast City Hospital. PATIENTS: Adult (over 16 years) CF patients with chronic (more than 4 years) B. cepacia complex infection who attended the Belfast City Hospital between January 1997 and November 1998. MEASUREMENTS: Forced expiratory volume in 1s, forced vital capacity, forced expiratory flow rate 25-75, C-reactive protein, leucocyte count and body mass index were measured before and after two weeks of treatment and analysed for any differences in change between the two episodes. RESULTS: All variables in both groups improved following treatment except for body mass index, which remained unchanged. No significant differences between the measurements were identified on comparison of single (monomicrobial) and multiple (polymicrobial) isolate episodes. CONCLUSION: Patients with chronic B. cepacia infection who develop a pulmonary exacerbation improve, as reflected by clinical and biochemical markers, following IV antibiotic treatment. Pulmonary exacerbations with multiple organisms are no more severe than those where only B. cepacia is isolated.     

Computed tomography correlates with pulmonary exacerbations in children with cystic fibrosis

RATIONALE: High-resolution computed tomography (HRCT) has been suggested as a potential outcome surrogate for cystic fibrosis (CF) lung disease. An important attribute of a valid outcome surrogate is that the surrogate reflects true clinical outcomes. OBJECTIVES: We performed this study to validate HRCT, a proposed surrogate outcome measure for CF lung disease, against a true clinical outcome, the number of respiratory tract exacerbations occurring in 2 yr, and to assess the correlation of CT scores and pulmonary function tests (PFTs) with this clinical outcome. METHODS: CTs and PFTs were performed on 6- to 10-yr-old children at the beginning and end of a 2-yr study during which the number of exacerbations were recorded. Spearman correlations and Poisson models were used to assess the correlation of the number of exacerbations with baseline values and changes in PFTs and CT scores. MEASUREMENTS AND MAIN RESULTS: Nine of 61 subjects had a total of 22 respiratory tract exacerbations. At baseline, PFTs and four CT scores showed significant correlation with number of exacerbations, but no variable by itself predicted exacerbations with high accuracy. For change over the 2-yr period, three CT scores showed significant correlation with exacerbations, whereas no PFTs showed significant correlation. CONCLUSION: This is the first study showing correlation between CT and a true clinical outcome. Change in CT scores correlates moderately well with the number of exacerbation. Poor correlation between change in FEV1 and exacerbations suggests that HRCT may be a more appropriate outcome surrogate for longitudinal studies of young children.     

Update on treatment of pulmonary exacerbations in cystic fibrosis

PURPOSE OF REVIEW: This review will define pulmonary exacerbations in cystic fibrosis and explain their importance in the pathophysiology and progression of this condition. I will stress the importance of prevention, where this is possible, and prompt treatment, where prevention has failed. The management of chronic pulmonary infection with Pseudomonas aeruginosa will be discussed, together with other, less tenacious organisms. RECENT FINDINGS: Developments in the treatment of chronic pulmonary infection with P. aeruginosa include new data on antibiotic selection through sensitivity testing and alternative antibiotic dosing regimens. Therapies which target the P. aeruginosa biofilm will be discussed, including those which are currently in use (such as azithromycin) as well as those being evaluated in preclinical studies. Supportive care and the role of noninvasive ventilation are discussed. SUMMARY: The prevention and prompt treatment of pulmonary exacerbations is a central component of cystic fibrosis care.     

Neurotoxicity in adult patients with cystic fibrosis using polymyxin B for acute pulmonary exacerbations

We present four case reports that describe neurotoxicity experienced in adult patients with cystic fibrosis (CF) receiving intravenous polymyxin B. Paresthesia was observed after the first dose of polymyxin B in all patients. These symptoms resolved after discontinuation of polymyxin B and switching treatment to colistin. All four patients completed therapy with colistin without experiencing additional adverse reactions. This report contributes to the small body of literature currently available on the use of polymyxin B in the CF population.     

Energy balance during acute respiratory exacerbations in children with cystic fibrosis.

Acute respiratory exacerbations have been proposed to contribute to the negative energy balance which causes undernutrition in cystic fibrosis. However, no studies have measured their effect on all components of energy balance. The aim of this study was to measure the effect of an acute respiratory exacerbation on energy balance. Fourteen children (six females, eight males, mean+/-SD age 9.9+/-2.4 yrs) were studied when well and during the course of an acute respiratory exacerbation treated with intravenous antimicrobial therapy. The total energy expenditure was measured using the doubly-labelled water method, resting energy expenditure by ventilated hood indirect calorimetry, energy intake by household measures records, and fat malabsorption from measurements of dietary fat intake and faecal fat output. The exacerbation was associated with a significant reduction in energy intake (mean paired difference 47 kJ x kg of body weight(-1) x day(-1), p<0.01). Changes in fat malabsorption and resting energy expenditure were negligible. The absence of significant changes in body weight and composition, together with the trend towards lower total energy expenditure, suggested no marked negative energy balance during the exacerbation. In conclusion, treatment of acute respiratory exacerbation with intravenous antimicrobial therapy represents a relatively minor challenge to energy balance and nutritional status in children with cystic fibrosis.     

Radioaerosol assessment of lung improvement in cystic fibrosis patients treated for acute pulmonary exacerbations.

We compared bronchopulmonary distribution homogeneity of a radioaerosol before and after hospitalization in 20 patients with cystic fibrosis (CF) with pulmonary exacerbations in order to assess lung improvement. Deposition homogeneity was quantified in terms of skew (an index of distribution symmetry), derived from frequency distribution histograms generated from gamma camera images of the lungs following radioaerosol inhalation. Lower skew values indicate enhanced distribution homogeneity. Right lung skew (RLS) was significantly reduced following therapy (1.00 +/- 0.49 to 0.84 +/- 0.47), whereas skew in the left lung was unchanged (0.95 +/- 0.38 to 0.87 +/- 0.40). The reduction in RLS was significant in patients with Shwachman-Kulczycki (SK) clinical scores less than 50 (1.27 +/- 0.53 to 0.90 +/- 0.42), but not in patients with scores greater than 50 (0.81 +/- 0.38 to 0.80 +/- 0.52). These results indicate that treatment affected the right lung more than the left lung, particularly in patients with SK scores less than 50, and suggests that radioaerosol lung imaging may be valuable in identifying sites of impairment to be targeted during treatment. Statistically, skew was less sensitive an indicator of acute change than several other clinical indices that improved following hospital treatment.     

Infection with Burkholderia cepacia complex bacteria and pulmonary exacerbations of cystic fibrosis

BACKGROUND: Studies have shown that cystic fibrosis (CF) patients who are chronically infected with Burkholderia cepacia complex bacteria may potentially acquire new strains of B cepacia. Our objective was to determine whether pulmonary exacerbations of CF are associated with acquisition of new B cepacia strains or with B cepacia strain replacement. METHODS: Thirty-six patients from seven centers who were chronically infected with B cepacia complex bacteria were prospectively followed up over a 38-month period. Patients had sputum cultures performed every 3 months while clinically stable and at the time of a pulmonary exacerbation. Each B cepacia complex isolate was speciated by polymerase chain reaction amplification of the recA gene to determine species status and was genotyped by pulsed-field gel electrophoresis to determine strain type. RESULTS: Thirty-five of 36 patients (97%) had chronic infection with Burkholderia cenocepacia III-A during clinical stability. All 36 patients maintained the same species and strain of B cepacia complex at the time of exacerbation as was found during clinical stability. B cepacia complex isolates retrieved during exacerbations were significantly less susceptible to ciprofloxacin, chloramphenicol, piperacillin, meropenem, and tobramycin compared to isolates retrieved from the same patients during clinical stability. CONCLUSION: Adult CF patients infected with B cenocepacia maintain the same strain of B cenocepacia during exacerbations; pulmonary exacerbations are not caused by acquisition of a new B cepacia species or strain. B cepacia isolates retrieved during exacerbations may be more resistant to antibiotics.     

Changes in spirometry during consecutive admissions for infective pulmonary exacerbations in adolescent and adult cystic fibrosis.

Changes in spirometry during consecutive admissions for treatment of pulmonary infective exacerbations were studied in 45 patients (24 males, 21 females) with cystic fibrosis (CF) who had required five or more such admissions. Over the overall study period there was a mean (SD) decline in FEV1 of -112.1 (188.0) ml yr-1 (P less than 0.001) and in FVC of -47.9 (82.4) ml yr-1 (P less than 0.001). FEV1 and FVC increased during each admission with treatment; however, the magnitude of this change became less over consecutive admissions by a mean value of -33.3 ml (45.0) (P less than 0.001) for FEV1, and -26.0 (72.2) ml (P less than 0.05) for FVC. In the majority of patients that died or underwent transplantation, FEV1 at the time of the last admission did not rise above 800 ml despite full treatment.